摘要:

AbstractThis study is based on the assumption that the distribution of age‐at‐diagnosis (a synonym for the incubation period) of a disease can convey information with respect to its pathogenetic mechanisms. To this end, an analysis of 3 retinobastoma (RB) international data sets was undertaken The molecular and cellular basis of RB is well understood and may serve our purpose well. RB is broken down into familial bilateral, unilateral, and sporadic unilateral form. Survival and hazard functions were computed. Several competing stochastic models (up to 9 per RB form) were fit. Each conveyed a meaningful pathogenetic mechanism. Between‐model discrimination was achieved by examining chi‐square goodness‐of‐fit values to select the best fitting model. Well‐known survival models, such as the simple exponential and the lognormal (Sartwell model) were ruled out. Age‐at‐diagnosis of familial RB proved to be best explained by 2 interfering exponentials (a diffonential function); the logistic was retained as the best adjusted model of the incubation period of sporadic cases of RB. As to familial unilaterals, both the diffonential and the logistic models fit equally well. The 3 data sets are consistent in these results, ruling out the less well‐fit competing models The results suggest the existence of 2 opposing but independent balancing internal mechanisms at the origin of familial RB. Sporadic RB appears to be due to a single host‐dependent self‐limiting cellular mechanism. Familial unilaterals which share both of these component mechanisms would involve lower retinoblast turnover rate. The cellular implications of these findings are discussed with regard to the relative importance of endogenous and exogenous induction factors in RB. It is concluded that, according to the RB form, RB occurrence results from 2 cellular interfering forces of different strength and organization.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractChoosing the best post‐mortem biological tissue source for chromosomal studies is challenge for cytogeneticists. Acceptable cytogenetic results are difficult to obtain from macerated and necrosed tissues.This report describes a method that is carried out after enzymatic digestion of cartilage from human fetuses and infants. It is currently employed successfully in our laboratory and our experience has shown that human cartilage could well be the tissue of choice for cytogenetic studies in stillborn fetuses and dead infants. © 1993 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractIn 1970, Sandrow et al. (J Bone Joint Surg 52‐A:363–370) described a syndrome of ulnar and fibular dimelia with facial abnormalities present in 2 generations in a family. We describe a new patient with similar manifestations, establishing this constellation of anomalies as a distinct syndrome. © 1993 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe report on a father and daughter with mirror hands and feet and a distinct nasa defect and compare their condition to a similar one reported previously in one other family. © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractMegalocornea (corneal diameter ≥ 13 mm) is associated with mental and neurological impairment, and minor anomalies in Neuhäuser syndrome (megalocornea‐mental retardation syndrome). Here we report 4 new cases of megalocornea and mental retardation. Those unrelated patients have a consistent pattern of anomalies with possible recessive inheritance which clearly differs from that of the original patients of Neuhäuser et al. [1975]. We discuss the heterogeneity of the syndromes with megalocornea and mental retardation. Based on these caes and on a review of the literature, we suggest a provisional clinically oriented classification in 5 subtypes: (1) a recessive form type Neuhäuser (with iris hypoplasia and minor anomalies), (2) a recessive form type Frank‐Temtamy (with camptodactyly, scoliosis and growth retardation), (3) a recessive type 3 including our 4 personal cases (with normal irides, severe hypotonia, relative or absolute macrocephaly and minor anomalies), (4) a possible Frydman type (with normal irides, megalencephaly and obesity), and (5) provisionally unclassifiable cases. © 1993 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe report on a male with brachydactyly, thin habitus with narrow shoulders, mesomelic shortness of the arms, long lower face with obtuse mandibular angle, maxillary hypoplasia with beaking of the nose, aortic root dilatation, and mitral valve prolapse. This combination of findings has not been reported previously. © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractRett syndrome consists of a characteristic progressive encephalopthy in females. The cause of this syndrome is unknown. We present a patient with 18q‐mosaicism who, along with the characteristics of this autosomal deletion, also fulfills the clinical criteria for Rett syndrome. This may demonstrate heterogeneity within this as yet cinically defined syndrome. A thorough chromosomal analysis should be performed in suspected cases of Rett syndrome. © 1993 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractProteus syndrome is and overgrowth syndrome principally affecting cutaneous and skeletal tissues, accompanied by subcutaneous hamartomas. We report on a patient with predominantly skeletal and visceral involvement, including a cardiac mass and thickening of the myocardial septum affecting cardiac conduction and contraction. © 1993 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractExperimental studies in chick embryos have demonstrated that truncus arteriosus (TA), a form of conotruncal cardiac defect, is due to abnormalities in the cranial neural crest. However, no data are available to support this hypothesis in humans with isolated TA. In the present study, the assessment of calcitonin immunoreactive cells (C‐cells) has been employed to evaluate whether or not the proportion of thyroid cells derived from the cranial neural crest is normal in patients with isolated TA. Thyroid sections from 15 such patients in which no other extracardiac malformations were neither clinically nor pathologically found, and from 11 control age‐matched patients were studied immunohistochemically at autopsy in order to determine the number and distribution of calcitonin‐containing cells. The volume density of C‐cells (0.888%) and the number of C‐cells per follicle (0.991) was significantly lower in patients with TA than in control patients (3.475%, and 2.367, respectively). The decrease of neural crestderived cells in the thyroid of patients with “isolated” TA documents more extent abnormalities than clinically suspected and supports the hypothesis of neural crest disturbance as the pathogenetic factor responsible for this heart malformation. © 1993 W

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractLinked markers are useful in prenatal diagnosis as well as presymptomatic diagnosis in late age‐of‐onset diseases such as Huntington disease (HD). It is widely assumed that most laboratory or clerical errors will be detected because of incompatibility of marker haplotypes within the family. However, errors in marker phenotypes that are compatible but wrong may result in a consultand being given an incorrect risk estimate. We have addressed this issue using simulated marker data in pedigress similar to those seen in our HD testing program. In Family Structure I (an 11‐member, 3‐generation family), a particular family was more likely to be detected as inconsistent than incorrectly assigned. In a small nuclear family (Family Structure IV), Fewer errors would be detected, and more would appear consistent but give incorrect risk estimates (e.g., low risk misclassified as noninformative or high). Given the presence of tight linkage, risk estimates are often calculated based on a small number of relatives. However, these computer simulations demonstrated that increasing the number of relatives types decrease the probability that the family will remain consistent with an error present, and, therefore, decreases the probability of an incorrect assignment of risk. It is important to decrease the level of such errors by duplicated readings of raw marker data and validation of computer input. © 1993 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320460211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY